title: Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis.
abstract: The Hippo tumor suppressor pathway plays important roles in organ size control through Lats1/2 mediated phosphorylation of the YAP/TAZ transcription co-activators. However, YAP/TAZ independent functions of the Hippo pathway are largely unknown. Here we report a novel role of the Hippo pathway in angiogenesis. Angiomotin p130 isoform (AMOTp130) is phosphorylated on a conserved HXRXXS motif by Lats1/2 downstream of GPCR signaling. Phosphorylation disrupts AMOT interaction with F-actin and correlates with reduced F-actin stress fibers and focal adhesions. Furthermore, phosphorylation of AMOT by Lats1/2 inhibits endothelial cell migration in vitro and angiogenesis in zebrafish embryos in vivo. Thus AMOT is a direct substrate of Lats1/2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Peilu
authors.initials: P
authors.lastname: She
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Fangtao
authors.initials: F
authors.lastname: Chi
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Jin
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiaocan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0815.
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Tao P
authors.initials: TP
authors.lastname: Zhong
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Biology, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: binzhao@zju.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000091082:Angiomotins; D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D000090683:Hippo Signaling Pathway; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D018919:Neovascularization, Physiologic / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D000199:Actins; D000091082:Angiomotins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C423985:AMOT protein, human; C092745:LATS1 protein, human; C406449:LATS2 protein, human; C541414:stk3 protein, zebrafish; D000099317:Hippo Kinases
keywords: AMOT; Actin; Angiogenesis; Cell Migration; Lats; Protein Kinase; Protein Kinases; Protein Phosphorylation; the Hippo Pathway